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5 December 2013 11:26 am ,
Vol. 342 ,
Dyslexia, a learning disability that hinders reading, hasn't been associated with deficits in vision, hearing, or...
Exotic, elusive, and dangerous, snakes have fascinated humankind for millennia. They can be hard to find, yet their...
Researchers have sequenced and analyzed the first two snake genomes, which represent two evolutionary extremes. The...
Snake venoms are remarkably complex mixtures that can stun or kill prey within minutes. But more and more researchers...
At age 30, Dutch biologist Freek Vonk has built up a respectable career as a snake scientist. But in his home country,...
Since arriving on the island of Guam in the 1940s, the brown tree snake ( Boiga irregularis ) has extirpated native...
An animal rights group known as the Nonhuman Rights Project filed lawsuits in three New York courts this week in an...
Researchers have been hot on the trail of the elusive Denisovans, a type of ancient human known only by their DNA and...
- 5 December 2013 11:26 am , Vol. 342 , #6163
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Inflammatory Enzyme's Bare Bones
4 December 1997 7:00 pm
Enzymes called lipoxygenases stoke the fires of inflammatory diseases such as asthma, atherosclerosis, psoriasis, and inflammatory bowel disease. In today's issue of Nature Structural Biology, researchers describe the first clear structure of a mammalian lipoxygenase. With this and similar blueprints, pharmaceutical companies should have an easier time designing lipoxygenase inhibitor drugs to douse the immune system's response in such diseases.
All lipoxygenases perform the same task: They attach two oxygen atoms to the long tail of a cell membrane molecule called arachodonic acid. Until now, the only known lipoxygenase structure was from a soybean plant--of dubious help to drug designers. So Michelle Browner of the biotech company Roche Bioscience in Palo Alto, California, and colleagues at Roche and the University of California, San Francisco (UCSF), decided to pin down the structure of 12-lipoxygenase, a mammalian version of particular interest because of its suspected role in the arterial damage that leads to blood clots.
The team used the tried-and-tested technique of x-ray crystallography: They formed a rabbit version of the enzyme into a crystal and scattered x-rays off it to deduce its structure. The researchers found that the globular enzyme's most important feature was a boot-shaped pocket containing the machinery that attaches the oxygen. This confirmed previous ideas that the long tail of the arachadonic acid penetrates into the pocket and the oxygen is attached part way up the tail.
This model still isn't universally accepted, says Colin Funk, a structural biologist at the University of Pennsylvania, Philadelphia. "There's still a bit of debate about how [arachadonic acid] might go into the pocket," he says. Some researchers have evidence that, with certain lipoxygenases, the molecule can slide into the pocket head first rather than tail first. Nevertheless, the structure should be a windfall for drug designers, says team member Robert Fletterick of UCSF. With "a little chemistry and some trial and error," they should be able to design drugs which mimic arachdonic acid, but plug the pocket.